Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway.

Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-3 (NLRP3)/caspase-1 classical pyroptosis pathway and intestinal flora in UC model rats. KJT components were analyzed using an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). A UC Sprague Dawley (SD) rat model was established using sodium dextran sulfate (DSS). Rats were randomly divided into four groups: control group (CG), UC model group (UG), KJT group (KG), and sulfasalazine (SASP) group (SG). After seven days of intervention, each group's body weight, disease activity index (DAI) scores, and colon length were recorded. Intestinal mucosal injury to each group was observed using hematoxylin-eosin staining. Additionally, we investigated the expression levels of NEK7, NLRP3, ASC, caspase-1, and GSDMD in intestinal mucosa, as well as serum interleukin- (IL-) 1ß, IL-18, and IL-33 proinflammatory factors. Intestinal microflora was analyzed using 16s rRNA sequencing. KJT controlled weight loss; decreased DAI scores; restored colon length; improved pathological injury in the colon; inhibited NEK7, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, and GSDMD-N expression; and decreased IL-1ß, IL-18, and IL-33 contents in UG rats' serum and colon tissue (P <0.001 or P <0.05). KJT also increased Ruminococcaceae, unclassified_f_Ruminococcaceae, and unclassified_g_Ruminococcus_1 levels and decreased Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Turicibacter, and uncultured_bacterium_g_Turicibacter levels. KJT alleviated UC immune-inflammatory responses to NLRP3/caspase-1 by inhibiting the NEK-7-activated classic pyroptosis pathway and improving intestinal microflora.

Mechanisms of indigo naturalis on treating ulcerative colitis explored by GEO gene chips combined with network pharmacology and molecular docking.

Oral administration of indigo naturalis (IN) can induce remission in ulcerative colitis (UC); however, the underlying mechanism remains unknown. The main active components and targets of IN were obtained by searching three traditional Chinese medicine network databases such as TCMSP and five Targets fishing databases such as PharmMapper. UC disease targets were obtained from three disease databases such as DrugBank,combined with four GEO gene chips. IN-UC targets were identified by matching the two. A protein-protein interaction network was constructed, and the core targets were screened according to the topological structure. GO and KEGG enrichment analysis and bioGPS localization were performed,and an Herbs-Components-Targets network, a Compound Targets-Organs location network, and a Core Targets-Signal Pathways network were established. Molecular docking technology was used to verify the main compounds-targets. Ten core active components and 184 compound targets of IN-UC, of which 43 were core targets, were enriched and analyzed by bioGPS, GO, and KEGG. The therapeutic effect of IN on UC may involve activation of systemic immunity, which is involved in the regulation of nuclear transcription, protein phosphorylation, cytokine activity, reactive oxygen metabolism, epithelial cell proliferation, and cell apoptosis through Th17 cell differentiation, the Jak-STAT and IL-17 signaling pathways, toll-like and NOD-like receptors, and other cellular and innate immune signaling pathways. The molecular mechanism underlying the effect of IN on inducing UC remission was predicted using a network pharmacology method, thereby providing a theoretical basis for further study of the effective components and mechanism of IN in the treatment of UC.

An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology.

AIM AND OBJECTIVE: Five-Flavor Sophora flavescens Enteric-Coated Capsules (FSEC) are the only proprietary Chinese medicine approved for the treatment of ulcerative colitis (UC) in China. Phase II and III clinical trials have shown that the curative effect of FSEC in relieving UC was not inferior to that of mesalazine granules and enteric-coated tablets, but its pharmacological mechanism is unclear. Therefore, the network pharmacology is used to reveal the more comprehensive effective components and targets of FSEC in the treatment of UC. METHODS: We screened the components of FSEC based on the TCMSP database, determined the action targets of these compounds through target fishing, and integrated the UC disease targets of several disease gene databases. The FSEC-UC composite targets were obtained by matching the two results, and then a PPI network was constructed to analyze the relationship between these targets, and the core targets were selected by topological correlation parameters. Finally, GO-BP and KEGG enrichment analyses were carried out using the clusterProfiler software package. RESULTS: One hundred and sixty active components of FSEC were identified and 77 targets were obtained. Of these, 30 core targets were the main targets of FESC in the treatment of UC. And quercetin, kaempferol, luteolin and mangiferin were regarded as the core active components of FSEC. The results screened by GO and KEGG enrichment analysis showed that FSEC played a comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation. CONCLUSION: The molecular mechanism of UC remission induced by FSEC was predicted by network pharmacology. These findings provide an important theoretical basis for further study of the effective substances and mechanism of FSEC in the treatment of UC.